Breast NeoplasmsPhase 1NCT01384253
Safety Study of ²¹²Pb-TCMC-Trastuzumab Radio Immunotherapy
A Phase 1 study testing ²¹²Pb-TCMC-Trastuzumab and trastuzumab in people with Breast Neoplasms and Peritoneal Neoplasms, run by Orano Med LLC at 2 sites in United States.
Trial summary
Monoclonal antibodies can transport and deliver radioactive elements capable of releasing sufficient amounts of energy to destroy tumor cells. In this clinical trial, we will study alpha particle radio immunotherapy using lead-212 (²¹²Pb), an isotope with a short path length targeted to malignant cells by the… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Breast Neoplasms, Peritoneal Neoplasms, Ovarian Neoplasms
- What is being tested?
- ²¹²Pb-TCMC-Trastuzumab and trastuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2011to Jul 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least 19 years of age.
- Life expectancy is greater than three months.
- Female subjects of child-bearing potential must have negative serum pregnancy test.
- If not surgically sterile, male and female patients of child-bearing potential must use double barrier contraception (e.g., hormonal; intrauterine device; barrier).
- Patients with HER-2 expressing tumors (e.g., ovarian, pancreatic, colon, gastric, endometrial, or breast) with measurable or non-measurable disease for which no standard therapy is available.
- HER-2 amplification by fluorescent in situ hybridization or HER-2 score of at least at least 1+ by Immunohistochemistry in more than 10% of the cells. Alternatively, HER-2 serum levels greater than 15ng/mL by ELISA.
- Disease must be predominantly intra-abdominal and should include documented peritoneal studding or positive peritoneal washings.
- Able and willing to sign an informed consent form.
Who cannot join
- ECOG performance status greater than 3.
- Any serious active disease or co-morbid condition that, in the opinion of the investigator, may interfere with the safety or the compliance with the study.
- Poor bone marrow reserve as defined by absolute neutrophil count less than 1.5 x 10³/cmm or platelets less than 100 x 10³/cmm within two weeks prior to initiation of treatment.
- Liver only metastases.
- Poor organ function as defined by one of the following:
- Total bilirubin greater than 1.5 upper limits of normal (ULN)
Show all 23Show fewer
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) greater than 2.5 ULN or greater than 5 ULN in case of documented liver metastasis
- Serum creatinine greater than ULN, except if calculated creatinine clearance greater than 60 mL/min
- Urine Protein/Creatinine Ratio greater than 1 on morning spot urinalysis or proteinuria greater than 500 mg/24 h
- Breast-feeding woman.
- No resolution of all specific toxicities (excluding alopecia) related to any prior anticancer therapy to Grade 2 according to the National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) v.4.03 or nausea and vomiting to Grade 3 and uncontrolled with anti-emetics.
- Wash out period of less than three weeks from previous anti-tumor therapy or any investigational treatment (and less than six weeks in case of prior nitroso-urea and or mitomycin C treatment) of scheduled date of administration.
- Wash out period of less than one week from last palliative dose of radiotherapy.
- Any other severe underlying medical conditions that could impair the ability to participate in the study or the interpretation of its results related to the investigational product such as:
- Patients with abnormal cardiac function defined by a left ventricular ejection fraction (LVEF) less than 50% by echocardiogram (ECHO) or multi gated acquisition (MUGA) scan
- Patients with previous history of acute cardiac failure
- Clinical symptoms of bowel obstruction, evidence of rectosigmoid bowel involvement on exam, or transmural bowel wall involvement on computed tomography (CT) or magnetic resonance imaging (MRI).
- Prior whole abdomen radiation therapy exceeding 4Gy, intraperitoneal radionuclide therapy, bone marrow transplant, or stem cell transplant.
- History of Human Immunodeficiency Virus (HIV) antibody by enzyme-linked immunosorbent assay (ELISA) or negative by Western blot (if ELISA is positive) or hepatitis B surface antigen (HBsAg) because of the potential for added toxicity from the radiolabeled antibody among patients infected with these viruses.
- Detectable human anti-human antibody (HAHA) if there is any history of monoclonal antibody exposure.
- Iodine allergy if the patient is unwilling to accept radiation to the thyroid from uptake of radionuclide without blocking.
- Allergy to furosemide if the patient is unwilling to accept radiation risk without these agents and alternative is not feasible.
- History of cumulative anthracycline therapy exceeding 200 mg/m² for doxorubicin or comparable low dose of other anthracyclines.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University Of Alabama at Birmingham
Birmingham, Alabama, 35233
UCSD Moores Cancer Center
San Diego, California
About this study
Official title: Phase I Trial of Intraperitoneal ²¹²Pb-TCMC-Trastuzumab for HER-2 Expressing Malignancy
Monoclonal antibodies can transport and deliver radioactive elements capable of releasing sufficient amounts of energy to destroy tumor cells. In this clinical trial, we will study alpha particle radio immunotherapy using lead-212 (²¹²Pb), an isotope with a short path length targeted to malignant cells by the trastuzumab antibody, as a potential treatment for metastatic diseases.
This Phase I trial is designed to determine the toxicity profile of ²¹²Pb-TCMC-Trastuzumab, its dose-limiting toxicities, and its anti-tumor effects in patients with HER-2 positive intraperitoneal cancers.
- Conditions
- Breast Neoplasms, Peritoneal Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Stomach Neoplasms
- Being tested
- ²¹²Pb-TCMC-Trastuzumab, trastuzumab
- Keywords
- HER2+, HER-2 positive, intraperitoneal, intra-abdominal, Lead 212, Radio Immunotherapy, Alpha particle, Antibodies, Immunoglobulins, Antibodies, Monoclonal, Immunologic Factors, Physiological Effects of Drugs, Pharmacologic Actions, RIT
- Medical subject headings
- Breast Neoplasms, Peritoneal Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
²¹²Pb-TCMC-TrastuzumabOther
The starting dose level will be 200 μCi/m² of ²¹²Pb-TCMC-Trastuzumab. Three to six patients will be treated at each dose level, and dose escalation will proceed if no more than 1 out of 6 patients in a cohort experiences dose limiting toxicity. Six patients will be treated at the maximum tolerated dose.
trastuzumabBiological
Also called Herceptin
4 mg/kg.
| Study group | Role | What they receive |
|---|---|---|
| Phase I: Dose escalation | Experimental | In preparation for the study, patients screened and eligible will have a peritoneal catheter placed and the evening prior to the injection of the labeled antibody will receive furosemide. Herceptin will be administered IV followed by a single IP infusion of ²¹²Pb-TCMC-Trastuzumab. Serial sampling of blood, urine, and dosimetry will be performed following treatment to determine the toxicity, pharmacokinetics, immunogenicity, and antitumor effects. Receives: Other: ²¹²Pb-TCMC-Trastuzumab; Biological: trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability: To measure the number of participants who experience adverse events after intraperitoneal (IP) administration of ²¹²Pb-TCMC-Trastuzumab.
Adverse events considered dose limiting toxicity:
- Grade 3 elevations of ALP, bilirubin, ALT, or AST lasting ≥7 days
- Grade 3 elevations of serum creatinine within 6 weeks of treatment
- Grade 2 elevations of serum creatinine lasting ≥7 days that occur after 6 weeks
- Grade 3 proteinuria
- Any other Grade 3 or 4 non-hematologic toxicity
- Grade 4 neutropenia lasting ≥7 days or febrile neutropenia of any duration
- Grade 3 thrombocytopenia that fails to recover to ≤ Grade 2 at 6 weeks
- Grade 4 thrombocytopenia lasting ≥7 days or thrombocytopenia accompanied by bleeding
Measured: Assessed periodically during study treatment follow-up, up to five years.
Secondary outcomes (3)
Immunogenicity: To characterize the human immune response against ²¹²Pb-TCMC-Trastuzumab given via IP infusion.
Measured: Assessed at six weeks visit
Anti-tumor effects: To monitor for anti-tumor effects as assessed by physical examination, radiographic imaging, and tumor marker studies.
Measured: Assessed after six and twelve weeks, and then at twelve-week intervals until progression.
Pharmacokinetics: To determine the plasma pharmacokinetics and assess the extent of exit of radioactivity from the peritoneal cavity by γ-camera imaging.
Measured: Up to 3 days post-injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2011 (estimated)
- Study startJul 2011
- Primary completionOct 2015
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Orano Med LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ruby F Meredith, M.D., Ph.D., Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01384253
- Sponsor's protocol ID
- AREVAMED01
- Status last verified
- Sep 2016
- First submitted
- 27 Jun 2011
- Last updated
- 30 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Meredith RF, Torgue J, Azure MT, Shen S, Saddekni S, Banaga E, Carlise R, Bunch P, Yoder D, Alvarez R. Pharmacokinetics and imaging of 212Pb-TCMC-trastuzumab after intraperitoneal administration in ovarian cancer patients. Cancer Biother Radiopharm. 2014 Feb;29(1):12-7. doi: 10.1089/cbr.2013.1531. Epub 2013 Nov 14.
PubMed 24229395Meredith R, Torgue J, Shen S, Fisher DR, Banaga E, Bunch P, Morgan D, Fan J, Straughn JM Jr. Dose escalation and dosimetry of first-in-human alpha radioimmunotherapy with 212Pb-TCMC-trastuzumab. J Nucl Med. 2014 Oct;55(10):1636-42. doi: 10.2967/jnumed.114.143842. Epub 2014 Aug 25.
PubMed 25157044
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Intraperitoneal ²¹²Pb-TCMC-Trastuzumab for HER-2 Expressing Malignancy
- ClinicalTrials.gov ID
- NCT01384253
- Acronym / sponsor ID
- AREVAMED01
- Conditions
- Breast Neoplasms, Peritoneal Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Stomach Neoplasms
- Keywords
- HER2+, HER-2 positive, intraperitoneal, intra-abdominal, Lead 212, Radio Immunotherapy, Alpha particle, Antibodies
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Orano Med LLCIndustry (pharma, biotech, devices)
- Study start
- Jul 2011
- Primary completion
- Oct 2015 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 29 Jun 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Monoclonal antibodies can transport and deliver radioactive elements capable of releasing sufficient amounts of energy to destroy tumor cells. In this clinical trial, we will study alpha particle radio immunotherapy using lead-212 (²¹²Pb), an isotope with a short path length targeted to malignant cells by the trastuzumab antibody, as a potential treatment for metastatic diseases.
This Phase I trial is designed to determine the toxicity profile of ²¹²Pb-TCMC-Trastuzumab, its dose-limiting toxicities, and its anti-tumor effects in patients with HER-2 positive intraperitoneal cancers.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase I: Dose escalation | Experimental | Other: ²¹²Pb-TCMC-Trastuzumab, Biological: trastuzumabIn preparation for the study, patients screened and eligible will have a peritoneal catheter placed and the evening prior to the injection of the labeled antibody will receive furosemide. Herceptin will be administered IV followed by a single IP infusion of ²¹²Pb-TCMC-Trastuzumab. Serial sampling of blood, urine, and dosimetry will be performed following treatment to determine the toxicity, pharmacokinetics, immunogenicity, and antitumor effects. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- At least 19 years of age.
- Life expectancy is greater than three months.
- Female subjects of child-bearing potential must have negative serum pregnancy test.
- If not surgically sterile, male and female patients of child-bearing potential must use double barrier contraception (e.g., hormonal; intrauterine device; barrier).
- Patients with HER-2 expressing tumors (e.g., ovarian, pancreatic, colon, gastric, endometrial, or breast) with measurable or non-measurable disease for which no standard therapy is available.
Key exclusion criteria (23 listed)
- ECOG performance status greater than 3.
- Any serious active disease or co-morbid condition that, in the opinion of the investigator, may interfere with the safety or the compliance with the study.
- Poor bone marrow reserve as defined by absolute neutrophil count less than 1.5 x 10³/cmm or platelets less than 100 x 10³/cmm within two weeks prior to initiation of treatment.
- Liver only metastases.
- Poor organ function as defined by one of the following:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ²¹²Pb-TCMC-TrastuzumabThe starting dose level will be 200 μCi/m² of ²¹²Pb-TCMC-Trastuzumab. Three to six patients will be treated at each dose level, and dose escalation will proceed if no more than 1 out of 6 patients in a cohort experiences dose limiting toxicity. Six patients will be treated at the maximum tolerated dose. | Other | Phase I: Dose escalation |
| trastuzumabAlso: Herceptin4 mg/kg. | Biological | Phase I: Dose escalation |
Primary outcome
Safety and tolerability: To measure the number of participants who experience adverse events after intraperitoneal (IP) administration of ²¹²Pb-TCMC-Trastuzumab.
Time frame: Assessed periodically during study treatment follow-up, up to five years.
Adverse events considered dose limiting toxicity: * Grade 3 elevations of ALP, bilirubin, ALT, or AST lasting ≥7 days * Grade 3 elevations of serum creatinine within 6 weeks of treatment * Grade 2 elevations of serum creatinine lasting ≥7 days that occur after 6 weeks * Grade 3 proteinuria * Any other Grade 3 or 4 non-hematologic toxicity * Grade 4 neutropenia lasting ≥7 days or febrile neutropenia of any duration * Grade 3 thrombocytopenia that fails to recover to ≤ Grade 2 at 6 weeks * Grade 4 thrombocytopenia lasting ≥7 days or thrombocytopenia accompanied by bleeding
3 secondary outcomes
Immunogenicity: To characterize the human immune response against ²¹²Pb-TCMC-Trastuzumab given via IP infusion.
Time frame: Assessed at six weeks visit
Anti-tumor effects: To monitor for anti-tumor effects as assessed by physical examination, radiographic imaging, and tumor marker studies.
Time frame: Assessed after six and twelve weeks, and then at twelve-week intervals until progression.
Pharmacokinetics: To determine the plasma pharmacokinetics and assess the extent of exit of radioactivity from the peritoneal cavity by γ-camera imaging.
Time frame: Up to 3 days post-injection
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2016.
- Background: PubMed 24229395Meredith RF, Torgue J, Azure MT, Shen S, Saddekni S, Banaga E, Carlise R, Bunch P, Yoder D, Alvarez R. Pharmacokinetics and imaging of 212Pb-TCMC-trastuzumab after intraperitoneal administration in ovarian cancer patients. Cancer Biother Radiopharm. 2014 Feb;29(1):12-7. doi: 10.1089/cbr.2013.1531. Epub 2013 Nov 14.
- Background: PubMed 25157044Meredith R, Torgue J, Shen S, Fisher DR, Banaga E, Bunch P, Morgan D, Fan J, Straughn JM Jr. Dose escalation and dosimetry of first-in-human alpha radioimmunotherapy with 212Pb-TCMC-trastuzumab. J Nucl Med. 2014 Oct;55(10):1636-42. doi: 10.2967/jnumed.114.143842. Epub 2014 Aug 25.
- AREVA Med's websiteLink provided by the sponsor.
- University of Alabama at Birmingham Department of Oncology Clinical ResearchLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ruby F Meredith, M.D., Ph.D. principal investigator
University of Alabama at Birmingham
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ²¹²Pb-TCMC-Trastuzumab and trastuzumab in people with Breast Neoplasms and Peritoneal Neoplasms, run by Orano Med LLC at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability: To measure the number of participants who experience adverse events after intraperitoneal (IP) administration of ²¹²Pb-TCMC-Trastuzumab. (time frame: Assessed periodically during study treatment follow-up, up to five years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01384253, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2016.